基于正交设计探索高尿酸血症大鼠模型的最佳配伍

Exploring the optimal compatibility of hyperuricemia rat model based on orthogonal design

目的通过正交设计探索果糖联合氧嗪酸钾(OAPS)构建高尿酸血症模型的最佳配伍,以期为高尿酸血症的干预及治疗提供理论依据。方法选取雄性SD大鼠20只,按照完全随机设计分为4个实验组和1个空白对照组,共5组,再根据三因素两水平正交设计表按照相应实验安排将实验组分为4个组[A1B1C1组采用5%果糖水+100 mg/(kg·d)OAPS灌胃;A1B2C2组采用5%果糖水+200 mg/(kg·d)OAPS腹腔注射;A2B1C2组采用10%果糖水+100 mg/(kg·d)OAPS腹腔注射;A2B2C1组采用10%果糖水+200 mg/(kg·d)OAPS灌胃)]。连续饲养8周,测量实验开始前、实验开始后第2、4、6、8周大鼠血清尿酸、肌酐、尿素氮水平,并对大鼠肝、肾组织进行病理切片观察。结果实验第8周,A1B1C1组大鼠血清尿酸水平显著高于其他各组(P<0.05)。实验第2周,血清尿素氮水平组间比较差异有统计学意义(P<0.05)。第8周时,A1B1C1组大鼠血清肌酐高于A2B2C1组(P<0.05)。病理切片显示肝、肾组织出现轻微损伤,但均属于正常可逆性损伤。正交设计结果表明整个实验中因素的影响排序为果糖浓度>OAPS给药途径>OAPS给药剂量。结论5%果糖水联合100 mg/(kg·d)OAPS灌胃能建立肝、肾损伤较轻的高尿酸血症大鼠模型。

Objective To explore the optimal combination of fructose and potassium oxazinate(OAPS)in the construction of hyperuricemia model through orthogonal design,so as to provide theoretical basis for the intervention and treatment of hyperuricemia.Methods Twenty male SD rats were strictly divided into four groups according to three factors and two levels(A1B1C1 group were 5%fructose water+100 mg/(kg·d)OAPS gavage,A1B2C2 group were 5%fructose water+200 mg/(kg·d)OAPS intraperitoneal injection,A2B1C2 group were 10%fructose water+100 mg/(kg·d)OAPS intraperitoneal injection,A2B2C1group were 10%fructose water+200mg/(kg·d)OAPS gavage),and an additional control group was added.The rats were fed for 8 weeks.Serum uric acid(UA),serum creatinine(Scr)and blood urea nitrogen(BUN)levels of rats were measured before experiment and at the 2nd,4th,6th and 8th weeks after experiment,and the pathological sections of liver and kidney tissues were observed.Results At the 8th week of experiment,the UA levels in the A1B1C1 group were significantly higher than those in other groups(P<0.05).In the 2nd week of experiment,there was an inter group difference in BUN levels(P<0.05).In the 8th week,the Scr in the A1B1C1 group was higher than that in the A2B2C1 group(P<0.05).The pathological section showed slight damage to the liver and kidney tissues,but both belonged to normal reversible damage.From the visual results of the orthogonal design,the order of influencing factors in the whole experiment was:concentration of fructose>administration methods of OAPS>dosage of OAPS.Conclusion 5%fructose water combined with 100mg/(kg·d)OAPS by gavage can establish the hyperuricemia rat model with slight damage to the liver and kidney tissues.